TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation

Cardiac Arrest Clinical Trial

— TELSTAR  

Official title:

TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02056236
• Other study ID #: NEF-14-18
• Secondary ID: NL46296.044.13
• Status: Completed
• Phase: N/A
• Start date: April 2014
• Est. completion date: January 24, 2022

Study information

• Verified date: February 2022
• Source: University of Twente
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to estimate the effect of medical treatment of electro-encephalographic status epilepticus on neurological outcome of patients with postanoxic encephalopathy after cardiac arrest.

Description:

Rationale: Electroencephalographic status epilepticus is described in 9-35% of patients with postanoxic encephalopathy after cardiac arrest and is associated with case fatality rates of 90-100%. It is unclear whether (some) electroencephalographic seizure patterns in these patients represent a condition which can be treated with antiepileptic drugs to improve outcome, or have to be regarded as an expression of severe ischemic damage, in which treatment with antiepileptic would be futile. Therefore, both treatment with and treatment without antiepileptic drugs are considered standard modalities in these patients. We aim to compare these standard strategies and hypothesize that aggressive and early treatment of electro-encephalographic status epilepticus with antiepileptic drugs improves outcome as compared to treatment without these drugs.

Objective: To estimate the effect of medical treatment of electro-encephalographic status epilepticus on neurological outcome of patients with postanoxic encephalopathy after cardiac arrest

Study design: We will perform a multicenter clinical trial with randomized treatment allocation, open label treatment and blinded endpoint evaluation (PROBE design). The intervention contrast will be aggressive medical treatment vs. no treatment of electroencephalographic status epilepticus, in addition to standard best medical management of comatose patients after cardiac arrest, including mild therapeutic hypothermia.

Study population: The study population will consist of adult patients with postanoxic encephalopathy after cardiac arrest, admitted to the intensive care unit, with electroencephalographic status epilepticus on continuous EEG, who are eligile for inclusion in this trial.

Intervention: Treatment of electroencephalographic status epilepticus will be based on guidelines for treatment of overt status epilepticus. The objective of this treatment will be to suppress all epileptiform activity in the EEG. If the electroencephalographic status epilepticus will return after tapering sedative treatment at 24 hours, the procedure will be repeated. If the status will return after 2 x 24 hours, it will be considered refractory.

Main study parameters/endpoints: The primary outcome measure will be neurological outcome defined as the score on the Cerebral Performance Category (CPC) at 3 months dichotomized as good (CPC 1-2 = no or moderate neurological disability) and poor (CPC 3-5 = severe disability, coma, or death).

Sample size: With a presumed reduction of poor outcome of 7%, from 99% - 92%, alpha of 5%, power of 80%, one tailed testing, and one interim analysis by an independent data safety and monitoring board, the objected number of inclusions is 172. With an estimation of an incidence of electroencephalographic status epilepticus of 20% in patients with postanoxic coma, the total number of patients to be monitored will be 860.

Nature and extent of the burden and risks associated with participation: Medical treatment of electroencephalographic status epilepticus may modify the high risk of death. Otherwise, this treatment of electroencephalographic status epilepticus may lead to prolonged hospitalization of several days of comatose patients that otherwise would have died. The risk of an increase of morbidity or mortality on the longer term is considered negligible.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 172
• Est. completion date: January 24, 2022
• Est. primary completion date: April 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients after cardiac arrest with suspected postanoxic encephalopathy

• Age 18 years or older

• Continuous EEG with at least eight electrodes started within 24 hours after cardiac arrest

• Electroencephalographic status epilepticus on continuous EEG

• Possibility to start treatment within three hours after detection of electroencephalographic status epilepticus.

Exclusion Criteria:

• A known history of another medical condition with limited life expectancy (<6 months)

• Any progressive brain illness, such as a brain tumor or neurodegenerative disease

• Pre-admission Glasgow Outcome Scale score of 3 or lower

• Reason other than neurological condition to withdraw treatment

• Follow-up impossible due to logistic reasons

Related Conditions & MeSH terms

• Anoxic Encephalopathy
• Brain Diseases
• Cardiac Arrest
• Heart Arrest
• Hypoxia, Brain
• Status Epilepticus

Intervention

Drug:
• Anti-epileptic drugs
Recommendations for the treatment of status epilepticus are based on recent international guidelines for treatment of overt status epilepticus. The objective of treatment with AED is to suppress all epileptiform activity. There is no clear proof that induction of a burst-suppression pattern is of additional value and induction of burst suppression is therefore not obligate. If the electroencephalographic status epilepticus returns after tapering sedative treatment at 24 hours, the procedure will be repeated. If the status returns after 2 x 24 hours, it will be considered refractory. Decisions regarding limitation or withdrawal of treatment will be done in accordance with the Dutch guideline "postanoxic coma". Reasons for withdrawal of treatment will be documented.

Other:
• No anti-epileptic drugs
The non-intervention group will be treated conform standard guidelines of treatment of comatose patients after cardiac arrest, but without anti-epileptic drugs or EEG based deep sedation. Treatment to suppress clinical myoclonia or seizures with low dose propofol is left to the discretion of the treating physician. Decisions regarding limitation or withdrawal of treatment will be done in accordance with the Dutch guideline "postanoxic coma". Reasons for withdrawal of treatment will be documented.

Locations

Country	Name	City	State
Belgium	Hôpital Erasme - Université libre de Bruxelles	Brussels	Lenniksebaan 808
Netherlands	Academic Medical Center	Amsterdam	Meibergdreef 9
Netherlands	Rijnstate Hospital	Arnhem	Wagnerlaan 55
Netherlands	Medisch Spectrum Twente	Enschede	Haaksbergerstraat 55
Netherlands	University Medical Center Groningen	Groningen	Hanzeplein 1
Netherlands	Maastricht UMC+	Maastricht
Netherlands	St. Antonius Hospital	Nieuwegein	Koekoekslaan 1
Netherlands	Canisius-Wilhelmina Hospital	Nijmegen
Netherlands	Radboud University Medical Center	Nijmegen	Geert Grooteplein-Zuid 10
Netherlands	Maasstad Hospital	Rotterdam	Zuid-Holland
Netherlands	VieCuri Medical Centre	Venlo	Tegelseweg 210

Sponsors (12)

Lead Sponsor	Collaborator
University of Twente	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Canisius-Wilhelmina Hospital, Maasstad Hospital, Maastricht University Medical Center, Medisch Spectrum Twente, Radboud University Medical Center, Rijnstate Hospital, St. Antonius Hospital, Université Libre de Bruxelles, University Medical Center Groningen, VieCuri Medical Centre

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (1)

Ruijter BJ, van Putten MJ, Horn J, Blans MJ, Beishuizen A, van Rootselaar AF, Hofmeijer J; TELSTAR study group. Treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation (TELSTAR): study protocol for a randomized controlled trial. Trials. 2014 Nov 6;15:433. doi: 10.1186/1745-6215-15-433. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurological outcome	The primary outcome measure will be neurological outcome defined as the score on the Cerebral Performance Category (CPC) at 3 months dichotomized as good (CPC 1-2 = no or moderate neurological disability) and poor (CPC 3-5 = severe disability, coma, or death).	three months
Secondary	Long term outcome	Secondary outcome measures will include i) mortality; ii) the CPC score at 6 and 12 months; iii) length of stay on the ICU; iv) duration of mechanical ventilation; v) seizure recurrence within one year; vi) quality of life as measured by the Medical Outcomes Study 36-item short-form health survey (SF36), depression as measured by the Montgomery and Åsberg Depression Rating Scale (MADRS) , and cognitive functioning as measured by detailed neuropsychological examination after 12 months.; Secondary outcome measures in survivors will be collected to thoroughly assess outcome and quality of life of survivors. These outcome measures will not be collected to test between-group differences, since the estimated number of survivors is small.; Furthermore, a limited amount of data on the use of resources will be collected for analysis of cost-effectiveness, including place of residence at one year and admission in hospitals, rehabilitations centers, and nursing homes within the first year.	12 months

External Links

•   TELSTAR trial website (English version)